Antihistamines Serotonin Agonists

Histamine Antagonists H 1 receptors inhibit smooth muscle contraction decrease wheal, flare,and itch decrease secretions: salivary and lachrymal CNS: sedation H 2 receptors inhibit gastric acid secretion decrease content and volume of gastric juice fasting, food stimulated and nocturnal

H 1 antagonists Relief of manifestations of immediate-type hypersensitivity reactions –allergic rhinitis –cold remedies newer agents “selective” for peripheral H 1 receptors –less sedation (dose dependant)

Antihistamine Products sedating –diphenhydramine (Benadryl) –chlorpheniramine (Chlor-Trimeton) non-sedating –fexofenadine (Allegra) –loratadine (Claritin) –cetirizine (Zyrtec)* * metabolite sedating

Sedation dose related even for newer agents most common ingredient in OTC sleep aids

Children’s Formulations Most available as syrups Allegra –30 mg tab Claritin –10 mg Redi-tab (fast dissolve)

Role of Antihistamines in the Treatment of Allergic Rhinitis

Nasal Steroids vs. Antihistamines

UCDHS Adult Allergic Rhinoconjunctivitis Guidelines HealthNet: Nasonex, Nasacort Pacificare: Rhinocort, Nasonex, Nasarel WHA: Rhinocort, Nasonex, Nasacort AQ Approved UCDMG P&T Committee January 2001 Reviewed by: T. Albertson S. Teuber, M. E. Gershwin, R. Mowers, J. Fischer January 2001

other routes of administration azelastine (Astelin) –nasal spray –allergic rhinitis –decrease side effect profile Bitter amine taste sedation (systemic absorption) olopatadine (Patanol) emedastine (Emadine) ophthalmic antihistamine H 1 allergic conjuctivitis and itching headache, taste perversion, abnormal dreams

H 2 Antagonists Therapeutic Indications –duodenal and gastric ulcer –gastroesophageal reflux disease (GERD) –erosive esophagitis –hypersecratory conditions –heart burn, indigestion, sour stomach –multidrug regimen for the eradication of H.Pylori in peptic ulcer disease

UC Davis Primary Care Adult Tx: GERD DrugAWP/ea Protonix ® 40 mg3.00 Aciphex ® 20 mg3.70 Prevacid ® 30 mg3.88 Nexium ® 20 mg3.99 Prilosec ® 20 mg4.15 Reviewed by; T. Albertson, J. Lee, J. Fischer, R. Mowers UCDMC P&T Committee January 2002 June 2001 Beck IT et al. The Second Canadian Consensus Conf. on Management of Patients with GERD. Can J Gastroenterol 1997;11 suppl B Katz PO. Treatment of GERD: Use of Algorithms. Am J Gastroenterol 1999;94(11)suppl:3-10.

Adverse Reactions low incidence of side effects headache and fatigue - 1% cimetidine –highest incidence of gynecomastia (1- 4%) –P450 drug interactions decrease digoxin levels increase flecainide activity

Serotonin 5-HT1 agonists Treatment of Migraine with or without aura. Acute treatment of Cluster headaches. Drugs are combination of 5-HT (1A, 1B, 1D, 1E, 1F, 7) No activity at 5HT 2-4 receptors, adrenergic, muscarinic, dopaminergic

Mechanism of Action Stimulation 5HT-1 receptors in extracerebral and intracranial blood vessels results in vasoconstriction. Also seen is an inhibition of neuropeptide release and decreased transmission in trigeminal pain pathways. It is thought cranial vessel dilation induced by release of vasoactive peptides from sensory nerve endings in an active trigeminal system my be a root cause of Migraine.

Prototype agents sumatriptan (Imitrex) –Tablets, nasal spray, injection rizatriptan (Maxalt) Several others

Common adverse events Generally well tolerated Events with 5% rate: paresthesia, nausea, dizzsiness, fatigue, dry mouth, headache, flushing Rare but serious events: cardiac events with fatalities, cerebrovascular events with fatalities (hemorrhage, stroke, others)

Rebound headache The risk of rebound headaches increases with the number of doses taken. Patient information: –Take as soon as possible –Second dose may be taken if no response in 2 hours –Limit injections to 2 per 24 hours –Contact MD before taking additional doses if no response

Other drugs for Migraine Treatment Ergot alkaloids such as dihydroergotamine (Migranal, DHE 45) Migraine Prophylaxis –Beta blockers –Calcium channel blockers –NSAID –Valproate